TTF1-NP通过活化内质网应激CHOP通路抑制大鼠原发性肝癌的生长

发布时间：2018-08-06 11:42

【摘要】：目的探讨TTF1-NP对大鼠的原发性肝癌的抑制作用及机制。方法通过二乙基亚硝胺(Diethylnitrosamine, DEN)司断给药法建立大鼠原发性肝癌模型,将模型大鼠随机分为阿霉素组、模型组和TTF1-NP低(4 μg/kg)、中(8 μg/kg)、高(16 μg/kg)剂量组。给药方式为腹腔注射,在给药前后分别进行PET/CT检测观察大鼠肿瘤组织的变化情况；通过HE染色观察TTF1-NP干预大鼠原发性肝癌后肝脏的形态学变化；利用Western Blot技术检测TTF1-NP干预大鼠原发性肝癌后内质网应激CHOP通路主要调控蛋白GRP78, IRE-1, CHOP以及eIF2a的变化。结果1. PET/CT检测结果显示：经过DEN间断给药,大鼠肝脏出现明显棕红色区域,TTF1-NP给药后,棕红色区域面积变小。TTF1-NP各剂量组PET/CT检测SUV值在给药后均有所减少。2. TTF1-NP给药后大鼠肝脏形态学变化：肉眼可见模型组大鼠肝脏质地变硬,肿大明显,颜色变黄,布满了大小不一的结节,出血坏死明显；TTF1-NP给药组随着给药浓度的增加,肝脏表面逐渐光滑,结节减少变小。HE染色结果显示：模型组大鼠肝索排列不齐,细胞表现出严重异形性,细胞核形态不规则；TTF1-NP给药组随着剂量增加,肝小叶结构逐渐完整,肝细胞逐渐变小且异形性逐渐降低,炎性细胞减少。3. Western Blot检测结果显示：随着TTF1-NP给药浓度的增高,GRP78、eIF2a、 IRE1表达量逐渐增加,CHOP蛋白除了在TTF1-NP高剂量组中大量表达外,在其余组几乎不表达或表达很少。结论TTF1-NP可以抑制DEN诱发的大鼠原发性肝癌的生长,其作用机制与活化内质网应激的CHOP通路有关。
[Abstract]:Objective to investigate the inhibitory effect and mechanism of TTF1-NP on primary liver cancer in rats. Methods the rat model of primary liver cancer was established by diethylnitrosamine (Diethylnitrosamine, DEN) administration. The model rats were randomly divided into adriamycin group, model group and low (4 渭 g/kg), middle (8 渭 g/kg) and high (16 渭 g/kg) groups of TTF1-NP. Intraperitoneal injection was used to detect the changes of tumor tissue by PET/CT before and after administration, and the morphological changes of liver after TTF1-NP intervention were observed by HE staining. The changes of major regulatory proteins GRP78, IRE-1, CHOP and eIF2a in endoplasmic reticulum stress (ER) stress CHOP pathway after TTF1-NP intervention were detected by Western Blot technique. Result 1. The results of PET/CT test showed that after intermittent administration of DEN, the area of TTF1-NP in the liver of rats was obviously brown-red, and the area of TTF1-NP was smaller. The SUV value of TTF1-NP in each dose group was decreased after administration of TTF1-NP. Morphological changes of liver after TTF1-NP administration: the liver texture of the model group became hard, swelling was obvious, the color became yellow, and it was covered with nodules of different sizes. The bleeding and necrosis of TTF1-NP group increased with the increase of the administration concentration of TTF1-NP. The results of HE staining showed that the hepatic cords in the model group were not aligned and the cells showed severe heteromorphism. In the TTF1-NP group, the hepatic lobular structure was gradually complete with the increase of dose. Hepatocytes gradually became smaller and heteromorphous gradually decreased, inflammatory cells decreased. 3. The results of Western Blot showed that with the increase of TTF1-NP concentration, the expression of IRE1 protein increased gradually, except in the high dose group of TTF1-NP, the expression of chop protein was almost no or little in other groups. Conclusion TTF1-NP can inhibit the growth of rat primary liver cancer induced by DEN, and its mechanism is related to the activation of endoplasmic reticulum stress (CHOP) pathway.
【学位授予单位】：延边大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735.7

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